Major Update 2: Remdesivir for Adults With COVID-19
Authors: Josef Finsterer
Journal: Annals of Internal Medicine (2022)

LettersAugust 2022Major Update 2: Remdesivir for Adults With COVID-19FREEJosef Finsterer, MD, PhDJosef Finsterer, MD, PhDNeurology and Neurophysiology Center, Vienna, AustriaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L22-0211 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: I read with interest Kaka and colleagues' update (1) of a living review about remdesivir as a treatment for COVID-19 in adults who were hospitalized. The authors evaluated 5 randomized controlled trials (RCTs) and 2 subtrials. They concluded that remdesivir “probably results in little to no difference in mortality and increases the proportion of patients recovered,” “may reduce time to clinical improvement,” and “may lead to small reductions in serious adverse events but may result in a small increase in any adverse event.” This review is appealing but raises concerns.I do not agree that the only limitation of Kaka and colleagues' review is the difference in definitions of COVID-19 severity and outcomes among the included RCTs. A limitation not considered is the interaction between remdesivir and the other drugs administered to patients with COVID-19 and those that patients were regularly receiving before admission. Patients with COVID-19 who are hospitalized frequently experience polypharmacy not only for COVID-19 but also because they frequently have multiple morbidities. Effectiveness and adverse effect profile may strongly depend on interactions with other drugs, particularly those that are eliminated through the same pathway in the liver or kidney and that exert their effects by the same mechanisms as remdesivir.Another limitation not considered in the authors' calculations and evaluations is the adverse effects of remdesivir itself. Recent studies in 3 patients have shown that remdesivir can be associated with bradycardia and QTc prolongation (2). Bradycardia in these 3 patients did not respond to atropine (2). Heart rate returned to normal with discontinuation of remdesivir (2). Several studies have shown that remdesivir can be hepatotoxic and can elevate liver enzyme levels (3), as do other nucleoside analogues. Remdesivir can cause cellular stress responses and injuries in hepatocytes through drug–drug or alcohol–drug interactions. A study of 2922 reports related to remdesivir registered in the U.S. Food and Drug Administration Adverse Event Reporting System included 493 reports of renal/urinary adverse effects (4). Use of remdesivir was associated with an increased chance of reporting renal/urinary disorders regardless of sex and age (risk ratio, 2.53 [95% CI, 2.10 to 3.06]) (4). Data from individual safety reports from the World Health Organization database VigiBase about remdesivir showed that 2107 cases of neuropsychological adverse reactions were reported, such as anxiety, seizures, lethargy, agitation, ischemic stroke, and hemiparesis (5).Overall, Kaka and colleagues' review has limitations that challenge their results and interpretation. Real-world data about the efficacy and adverse effects of drugs need to be included before assessing their effectiveness and safety profile.References1. Kaka AS, MacDonald R, Linskens EJ, et al. Major update 2: remdesivir for adults with COVID-19. A living systematic review and meta-analysis for the American College of Physicians practice points. Ann Intern Med. 2022;175:701-9. [PMID: 35226522] doi:10.7326/M21-4784 LinkGoogle Scholar2. Shirvani M, Sayad B, Shojaei L, et al. Remdesivir-associated significant bradycardia: a report of three cases. J Tehran Heart Cent. 2021;16:79-83. [PMID: 35082876] doi:10.18502/jthc.v16i2.7390 CrossrefMedlineGoogle Scholar3. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395:1569-78. [PMID: 32423584] doi:10.1016/S0140-6736(20)31022-9 CrossrefMedlineGoogle Scholar4. Silva NAO, Zara ALSA, Figueras A, et al. Potential kidney damage associated with the use of remdesivir for COVID-19: analysis of a pharmacovigilance database. Cad Saude Publica. 2021;37:e00077721. [PMID: 34787281] doi:10.1590/0102-311X00077721 CrossrefMedlineGoogle Scholar5. Lee S, Yang JW, Jung SY, et al. Neuropsychological adverse drug reactions of Remdesivir: analysis using VigiBase, the WHO global database of individual case safety reports. Eur Rev Med Pharmacol Sci 2021;25:7390-7. [PMID: 34919240] doi:10.26355/eurrev_202112_27435 CrossrefMedlineGoogle Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Neurology and Neurophysiology Center, Vienna, AustriaDisclosures: Authors have reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L22-0211. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMajor Update 2: Remdesivir for Adults With COVID-19: A Living Systematic Review and Meta-analysis for the American College of Physicians Practice Points Anjum S. Kaka , Roderick MacDonald , Eric J. Linskens , Lisa Langsetmo , Kathryn Vela , Wei Duan-Porter , and Timothy J. Wilt Major Update 2: Remdesivir for Adults With COVID-19 Anjum S. Kaka and Timothy J. Wilt Metrics August 2022Volume 175, Issue 8Page: W81KeywordsCOVID-19Drug therapyInpatientsSystematic reviews ePublished: 16 August 2022 Issue Published: August 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...